Evidence map›Paper›PMID 20501660›Full record

ArticleThe Journal of biological chemistry2010

Methyl-beta-cyclodextrin suppresses hyaluronan synthesis by down-regulation of hyaluronan synthase 2 through inhibition of Akt.

Anne Kultti, Riikka Kärnä, Kirsi Rilla, Pertti Nurminen, Elina Koli, Katri M Makkonen, Jutong Si, Markku I Tammi, Raija H Tammi

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.0field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 34 citations in OpenAlex.

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  20. Immunopathogenesis of Graves' ophthalmopathy: the role of the TSH receptor.Best practice & research. Clinical endocrinology & metabolism · 2012
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Anne KulttiInstitute of Biomedicine, Anatomy, University of Eastern Finland, FIN-70211 Kuopio, Finland. anne.kultti@uef.fi
Riikka Kärnä
Kirsi Rilla
Pertti Nurminen
Elina Koli
Katri M Makkonen
Jutong Si
Markku I Tammi
Raija H Tammi
University of Eastern Finland · FIFred Hutch Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hyaluronan synthases (HAS1-3) are integral plasma membrane proteins that synthesize hyaluronan, a cell surface and extracellular matrix polysaccharide necessary for many biological processes. It has been shown that HAS is partly localized in cholesterol-rich lipid rafts of MCF-7 cells, and cholesterol depletion with methyl-beta-cyclodextrin (MbetaCD) suppresses hyaluronan secretion in smooth muscle cells. However, the mechanism by which cholesterol depletion inhibits hyaluronan production has remained unknown. We found that cholesterol depletion from MCF-7 cells by MbetaCD inhibits synthesis but does not decrease the molecular mass of hyaluronan, suggesting no major influence on HAS stability in the membrane. The inhibition of hyaluronan synthesis was not due to the availability of HAS substrates UDP-GlcUA and UDP-GlcNAc. Instead, MbetaCD specifically down-regulated the expression of HAS2 but not HAS1 or HAS3. Screening of signaling proteins after MbetaCD treatment revealed that phosphorylation of Akt and its downstream target p70S6 kinase, both members of phosphoinositide 3-kinase-Akt pathway, were inhibited. Inhibitors of this pathway suppressed hyaluronan synthesis and HAS2 expression in MCF-7 cells, suggesting that the reduced hyaluronan synthesis by MbetaCD is due to down-regulation of HAS2, mediated by the phosphoinositide 3-kinase-Akt-mTOR-p70S6K pathway.

Indexed as

beta-CyclodextrinsCell Line, TumorCholesterolDown-RegulationGlucuronosyltransferaseHumansHyaluronan SynthasesHyaluronic AcidPhosphatidylinositol 3-KinasesPhosphorylationProto-Oncogene Proteins c-aktRibosomal Protein S6 Kinases, 70-kDaRNA, MessengerSignal Transductionbeta-CyclodextrinsCholesterolGlucuronosyltransferaseHAS2 protein, humanHyaluronan SynthasesHyaluronic Acidmethyl-beta-cyclodextrinPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRibosomal Protein S6 Kinases, 70-kDaRNA, Messenger

Identifiers

PMID20501660
PMCPMC2906282
OpenAlexW2068425394

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.